Palladium-catalyzed allylating heteroannulation of o-alkynyl-allyloxybenzenes. A route to 2-substituted-3-allylbenzo[b]furans

Article abstract of DOI:10.1055/s-1998-1755

In the presence of palladium(0), o-alkynyl allyloxybenzenes produce 2-substituted 3-allylbenzo[b]furans in fair yields. This heteroannulation is promoted by the η³-allyl palladium species issued from early reaction of the catalyst with the starting allyl aryl ether.

Full text of DOI:10.1055/s-1998-1755

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LETTERS
SYNLETT
Palladium-Catalyzed Allylating Heteroannulation of o-Alkynyl-Allyloxybenzenes. A Route to
2-Substituted-3-Allylbenzo[b]furans
Nuno Monteiro and Geneviève Balme
Laboratoire de chimie organique I, associé au CNRS, Université Claude Bernard, CPE, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France.
Fax : (0)4.72.43.12.14; E-mail : balme@univ-lyon1.fr
Received 16 March 1998
Abstract: In the presence of palladium(0), o-alkynyl allyloxybenzenes
produce 2-substituted 3-allylbenzo[b]furans in fair yields. This
3
heteroannulation is promoted by the η -allyl palladium species issued
from early reaction of the catalyst with the starting allyl aryl ether.
Benzo[b]furans are of great interest due to their widespread occurrence
1
in nature as well as their remarkable physiological properties. Among
the various synthetic approaches developed toward the benzofuran
2
nucleus, recent efforts have focused on palladium catalyzed
3
heteroannulation processes involving acetylenic compounds. In
particular, cyclization of o-alkynylphenols promoted by σ-aryl(or vinyl)
palladium complexes has recently opened a valuable new route toward
4
2, 3-disubstituted benzo[b]furans. This annulation process can be seen
as an attack of the phenoxide onto the triple bond from the opposite side
of the activating σ-unsaturated palladium species generated from
oxidative addition of the palladium(0) complex to an unsaturated halide
Scheme 2
or triflate. A reductive elimination gives the cyclization product and
regenerates the catalyst (Scheme 1).
9
2
treatment with n-Buli and quenching with various electrophiles (H O,
Me SiCl, (MeO) SO ).
3
2
2
Scheme 1
As part of our ongoing interest in the development of conceptually
5
related processes aimed in particular at the synthesis of heterocycles,
we found that such annulation reaction can equally be effected by using
η3-allyl palladium complexes as activating species thus leading to 3-
6a
allylbenzofurans. Only in rare occasions has this type of activating
species been used in the past and it concerned the cyclization of
alkynylcarboxylic acids. We were aware of the fact that in the case of
Scheme 3
6b
o-alkynylphenols direct endo-dig cyclization might occur under basic
conditions to give the corresponding benzo[b]furans even in the absence
Compound 1f was prepared from 1a by coupling with allyl bromide in
the presence of catalytic copper iodide (Scheme 4).
3a,4
of catalysis.
We decided to avoid this potentially competitive
reaction by starting from o-alkynylallyloxybenzenes of type 1 taking
advantage of the ability of such species to form η3−allyl palladium
7
complexes. In this way, the allyl moiety would be internally delivered
allowing the reaction to occur in a complete neutral medium. A
reasonable reaction path is depicted in Scheme 2: oxidative addition of
the palladium(0) complex to and displacement of one ligand of the
1
resulting η3−allyl palladium species by the proximal triple bond would
allow activation and thus promote the attack of the phenoxide.
Subsequent coupling of the η3-allyl and the furanyl moiety would give 2
and regenerate the palladium(0) complex. We present herein our
successful preliminary results toward this goal.
Scheme 4
Acceptable rates of cyclization were obtained for 1c-f using Pd(PPh3)4
as catalyst (5 mol%) in a mixture of MeCN:THF (4:1) at 80°C (Table,
entries 3-6).The corresponding benzofurans were isolated in good yield
and only traces of products 3 resulting from direct cyclization were
formed in these reactions (Scheme 5). A longer reaction time was
needed in the case of allyl fragments bearing a substituent on the central
A range of o-alkynylallyloxybenzenes 1a-f were prepared and their
reactivity toward palladium catalysts studied. Compounds 1a-e were
readily synthesized in three steps as depicted in Scheme 3. The
6b
carbon (entry 5). In line with previous results and concerning the
cinnamyl group in 1d, the carbon-carbon bond formation toward the η3−
8
procedure is based on the Corey-Fuchs dibromomethylenation applied
to 2-allyloxybenzaldehydes derived from salicylaldehyde, followed by
allyl palladium species took place regioselectively to the less crowded

July 1998
SYNLETT
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allyl terminus. The stereochemistry of the allylic moiety in 2d was
found to be exclusively E (entry 4).
(2) Sundberg, R.J.; Van Nguyen, P. in "Progress in Heterocyclic
Chemistry", Vol. 5, H. Suschitzky and E. F.V. Scriven, Eds.,
Pergamon Press, 1993, p. 129.
(3) For leading references see a) Kundu, N.G.; Pal, M.; Mahanty, J.S.;
De, M. J. Chem. Soc., Perkin Trans. 1, 1997, 2815. b) Larock,
R.C.; Yum, E.K.; Doty, M.J.; Sham, K.K.C. J. Org. Chem., 1995,
60, 3270. c) Kondo, Y.; Shiga, F.; Murata, N.; Sakamoto, T.;
Yamanaka, H. Tetrahedron, 1994, 50, 11803. d) Arcadi, A.;
Cacchi, S. and Marinelli, F. Synthesis, 1986, 749.
Scheme 5
(4) Arcadi, A.; Cacchi, S.; Del Rosario, M.; Fabrizi, G. and Marinelli,
F. J. Org. Chem., 1996, 61, 9280.
(5) We and other groups have shown that the intramolecular attack of
nucleophiles to triple bonds can be promoted by various σ-
unsaturated organopalladium species; σ-alkynyl : Bouyssi, D.;
Goré, J.; Balme, G. Tetrahedron Lett., 1992, 33, 2811; σ-
(hydrido)alkynyl : Monteiro, N.; Goré, J.; Balme, G. Tetrahedron,
1992, 48, 10103. Marat, X.; Monteiro, N.; Balme, G. Synlett,
1997, 845; σ-allenyl : Bouyssi, D.; Goré, J.; Balme, G.; Louis, D.;
Wallach, J. Tetrahedron Lett., 1993, 34, 3129; σ-aryl(or vinyl) :
for representative examples see Inoue, Y.; Itom,Y.; Yen, J.F.;
Imaizumi, S. J. Mol. Catal., 1990, 60, L1-L3. Bouyssi, D.; Balme,
G.; Fournet, G.; Monteiro, N.; Goré, J. Tetrahedron Lett., 1991,
32, 1641. Luo, F.T.; Schreuder, I.; Wang, R.T.; J. Org. Chem.,
1992, 57, 2213. Saulnier, M.G.; Frenesson, D.B.; Deshpande,
M.S.; Vyas, D.M. Tetrahedron Lett., 1995, 36, 7841. Cavicchioli,
M.; Decortiat, S.; Bouyssi, D.; Goré, J.; Balme, G. Tetrahedron,
1996, 52, 11463. Arcadi, A. Synlett, 1997, 941. Bouyssi, D.;
Cavicchioli, M.; Balme, G. Synlett, 1997, 944. Cacchi, S.; Fabrizi,
G.; Moro, L. J. Org. Chem., 1997, 62, 5327. See also references
(4) and (6).
However cyclization of compounds 1a,b proved problematic (entries 1,
2), always giving rise to complex mixtures of products. In the case of 1a
it was nevertheless possible to identify the bis-allylic derivative 2f as the
only product possessing the expected 3-allylbenzo[b]furan structure, a
compound which could not be cleanly isolated. We thus believe that
10
(6) a) A similar strategy leading to the synthesis of 3-allylindoles has
been developed independently and simultaneously by Cacchi's
group: Cacchi, S.; Fabrizi, G.; Pace, P. J. Org. Chem., 1998, 63,
1001. b) Tsuda, T.; Ohashi, Y.; Nagahama, N; Sumiya, R. and
Saegusa, T. J. Org. Chem., 1988, 53, 2650. Mandai, T.; Ohta, K.;
Baba, N.; Kawada, M.; Tsuji, J. Synlett, 1992, 671.
competitive palladium-catalyzed allylation of the acetylenic moiety is
responsible for the unsuccessful cyclization of terminal acetylene 1a.
Unfortunately, rapid desilylation of 1b occurred under the same
cyclization conditions which again led to a complex mixture of
products. Further work will be undertaken in order to find conditions
allowing cyclization of terminal acetylenes.
(7) See Tsuji, J. "Palladium Reagents and catalysis"; John Wiley &
Sons, 1995, p. 328-329.
In conclusion, we have shown that 2-substituted 3-allylbenzo[b]furans
can be easily obtained from readily available o-alkynylallyloxy
(8) Corey, E. J.; Fuchs, P.L. Tetrahedron Lett., 1972, 13, 3769.
(9) Barton, T.J.; Groh, B.L. J. Org. Chem., 1985, 50, 158.
11
benzenes by simple treatment with a palladium catalyst. Although the
reaction is so far limited to the cyclization of internal alkynes we believe
that the simple procedure described herein will find wide application for
the elaboration of more complex molecules possessing the benzofuran
nucleus.
(10) Tsuda, T.; Chujo, Y.; Nishi, S-I.; Tawara, K.; Seagusa, T. J. Am.
Chem. Soc., 1980, 102, 6381. Inoue, Y.; Ohuchi, K.; Kawamata,
T.; Ishiyama, J-I.; Imaizumi, S. Chem. Lett., 1991, 5, 835.
(11) A representative experimental procedure is as follows: Pd(PPh )
3 4
(0.05 mmol) was added to a solution of the allyloxybenzene (1
References and Notes
mmol) in CH CN:THF (4:1; 5 ml) and the resulting mixture was
3
(1) Donnelly, D.M.X. and Meegan, M. J. in Comprehensive
Heterocyclic Chemistry, vol.4, pp. 657-712, ed. A.R. Katritzky
and C.W. Rees, Pergamon Press, Oxford, 1984. Cagniant, P.;
Cagniant, D., Adv. Heterocycl. Chem., 1975, 18, 343.
heated at 80°C till disappearance of the starting material (TLC).
The solvents were then removed in vacuo and the residue was
purified by flash chromatography on silica gel to give the pure
benzofuran.